Rationale: Southern Africa is where almost 30% of the approximately 40 million HIV-infected people in the world live, in an area estimated to have 2% of the global population. While an estimated two million men, women, and children are yet in urgent need of antiretroviral treatment in this region, close to 200,000 individuals are now believed by the World Health Organization to be receiving treatment. Answers are urgently needed to clinical and operational research questions regarding the most effective implementation and monitoring of wide-scale antiretroviral treatment delivery. Specific Aims: 1) To measure the effectiveness of antiretroviral therapy in southern Africa, and to describe factors that influence outcomes; 2) To improve the prognosis of people living with HIV and AIDS eligible for or initiating highly active antiretroviral treatment in southern Africa through timely and operative regional epidemiological evaluations; and 3) To increase the capacity for delivering antiretroviral therapy in this region by increasing the capacity for monitoring exposures and outcomes at the individual and population levels. Research Objectives: 1) To describe issues related to the provision of health care to children and adults in southern Africa, with a focus on the delivery of ART, waiting times and program level influences on survival and other outcomes, including losses to follow up; 2) To describe antiretroviral treatment issues in adults (including pregnant women) and children, with an emphasis on the monitoring of treatment response and prognostic factors, including exposure to drugs to prevent mother to child transmission of HIV, and adverse events associated with antiretroviral treatment; and 3) To describe issues related to important complications of HIV infection and antiretroviral therapy use, with a focus on tuberculosis, the immune reconstitution and inflammatory syndrome, and prophylaxis against life-threatening opportunistic infections. Research Design and Methods: The OASIS Collaboration includes 17 clinics and clinical cohorts in 6 countries in the region, involving 35,070 HIV-1 infected adults and children. We will use innovative and state-of-the-art statistical approaches to analyze data from this observational cohort study, including techniques which account for the longitudinal and hierarchical structure of the data. An operational structure is proposed that emphasizes the long-term collaborative and capacity-building approach of the collaboration.